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Publication
The role of apolipoprotein A-IV (apoA-IV) in regulating glucagon-like peptide
(GLP)-1 secretion.
Authors Wang F, Yang Q, Huesman S, Xu M, Li X, Lou D, Woods SC, Marziano C, Tso P
Submitted By Submitted Externally on 10/1/2015
Status Published
Journal American journal of physiology. Gastrointestinal and liver physiology
Year 2015
Date Published 8/1/2015
Volume : Pages Not Specified : ajpgi.0007
PubMed Reference 26294669
Abstract Both GLP-1 and apoA-IV are produced from the gut and enhance postprandial
insulin secretion. This study investigated whether apoA-IV regulates
nutrient-induced GLP-1 secretion and whether apoA-IV knockout causes
compensatory GLP-1 release. Using lymph-fistula-mice, we first determined
lymphatic GLP-1 secretion by administering apoA-IV prior to an intraduodenal
Ensure infusion. ApoA-IV changed neither basal nor Ensure-induced GLP-1
secretion relative to saline administration. We then assessed GLP-1 in
apoA-IV-/- and WT mice administered intraduodenal Ensure. ApoA-IV-/- mice had
comparable lymph flow, lymphatic triglyceride, glucose and protein outputs as WT
mice. Intriguingly, ApoA-IV-/- mice had higher lymphatic GLP-1 concentration and
output than WT mice 30-min after Ensure administration. Increased GLP-1 was also
observed in plasma of apoA-IV-/- mice at 30-min. ApoA-IV-/- mice had comparable
total gut GLP-1 content relative to WT mice under fasting, but a lower GLP-1
content 30-min after Ensure administration, suggesting that more GLP-1 was
secreted. Moreover, an injection of apoA-IV protein did not reverse the
increased GLP-1 secretion in apoA-IV-/- mice. Finally, we assessed gene
expression of glucose transporter-2 (GLUT2) and the lipid receptors, including
G-protein-coupled receptor (GPR) 40, GPR119, and GPR120 in intestinal segments.
GLUT2, GPR40 and GPR 120 mRNAs were unaltered by apoA-IV knockout. However,
ileal GPR119 mRNA was significantly increased in apoA-IV-/- mice. GPR119
co-localizes with GLP-1 in ileum and stimulates GLP-1 secretion by sensing
oleoyl-ethanolamide (OEA), lysophosphatidylcholine (LPC), and
2-monoacylglycerols. We suggest that increased ileal GPR119 is a potential
mechanism by which GLP-1 secretion is enhanced in apoA-IV-/- mice.




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